Celiprolol, a beta-adrenoceptor antagonist with vasodilator effect, improves hemodynamic response to catecholamine, spontaneous locomotor activity, and survival in cardiomyopathic hamsters with advanced heart failure.
To assess the effects of celiprolol, which is a selective beta1-antagonist with vasodilating properties, on chronic heart failure in the cardiomyopathic hamster UM-X7.1 (CMH), we studied survival in treated CMH (celiprolol, 100 mg/kg/day) and untreated CMH. We also measured the hamsters' locomotor activity (by using an Automex system), in vivo left ventricular (LV) pressure with or without dobutamine infusion, and the myocardial beta-adrenergic-receptor density (Bmax), all at the age of approximately 210 days. Survival was significantly improved in the treated group compared with untreated group by 33.4% at the age of 210 days, and the median probabilities of survival were age 252 days in the treated group and 203 days in the untreated group (p < 0.01). The locomotor activity count was significantly higher in the treated group (14,945+/-6,895) than in the untreated group (8,264+/-2,945 counts/day; p < 0.05). The response of LV peak +/-dP/dt to dobutamine was significantly improved in the treated group by 22.9 and 34.8%, respectively, at 18 microg/kg/min. Bmax was also higher in the treated group than in the untreated group (80.1+/-15.1 vs. 65.2+/-10.6 fmol/mg; p < 0.05). This study suggests that long-term treatment with celiprolol could improve both survival and the hemodynamic responses to dobutamine, associated with the upregulation of beta-receptors, and increased locomotor activity.
Nakamura
Y
Y
The Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Ryoke
T
T
Tanaka
N
N
Ohkusa
T
T
Matsuzaki
M
M
D000318:Adrenergic beta-Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D009202:Cardiomyopathies / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D017272:Celiprolol / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D006224:Cricetinae; D004280:Dobutamine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008647:Mesocricetus; D009043:Motor Activity / Q000187:drug effects*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects; D012083:Renin / Q000097:blood; D015996:Survival Rate; D016277:Ventricular Function, Left
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D017272:Celiprolol; D012083:Renin